The underlying basis for the rise in serum gonadotropins and a decline in ovarian function during menopause is not known. Earlier studies in the rat show that there is a steady decline of germinal structures in the ovary with age. Also, the incidence of acyclicity increases with age and is first demonstrable between 270 and 360 days of age in rats. This was shown to also be the time when serum levels of gonadotropins and PRL change. Between 270 and 360 days there is a two-fold decrease in LH, a four-fold increase in FSH and an eight-fold increase in PRL. Ultrastructural studies of pituitaries showed smaller gonadotropes and an increase in lysosomes and crinophagy that increases with age. Estradiol 17Beta and/or progesterone administration to castrate rat models was not as effective in the suppression of FSH and LH at 360 days and the facilitatory effect of these steroids was absent at this age as compared to 90 or 270 day old rats. A colony of CBA mice has recently been established in our laboratory. This strain of mouse is noted to exhibit a precocious termination of estrous cycles and reproduction. It will be determined whether these aged animals show changes in ovarian morphology and gonadotropin levels more analogous to those found at menopause. Radiommunoassays of serum FSH, LH and PRL will be determined in these animals as well as ovarian histology and pituitary ultrastructure. Since at 360 days rats show dramatic increases in FSH and PRL and a decrease in LH as compared to 270 day old rats, experiments will be conducted to determine the earliest age statistically significant changes in these parameters occur. Because serum PRL has increased dramatically at 360 days of age and this increase has at times been associated with acyclicity in various speciec, bromoergocryptine, a PRL inhibitor, will be administered to these animals and its effect on LH levels and cyclicity determined. Perphenazine, a compound that stimulates PRL secretion, will be administered to 270 day old cycling rats with low PRL levels to determine whether induced hyperprolactinemia causes a decrease in LH and acyclicity.